The possibility of genome sequencing by measuring the transverse conductivity upon applied DC bias while a DNA strand is translocated through a nanogap or nanopore has recently been the subject of debate based on theoretical considerations and experimental results. See, for example, R. Zikic et al, Phys. Rev. E 74, 011919 (2006); J. Lagerqvist et al, Nano Lett. 6, 779 (2006); M. Zwolak, and M. Di Ventra, Nano Letters 5, 421 (2005); and M. Zwolak, and M. Di Ventra, arXiv, cond-mat/0708.2724v1). The origin of the debate stems from the fact that the Fermi energy of gold electrodes at 0K is rather far (˜2 eV) from the molecular eigen-levels of the DNA nucleotides. The electronic transport is therefore dominated by non-resonant tunneling, which is highly dependent on the difficult-to-control relative geometry between the molecule and electrodes, while it is weakly dependent on the electronic structure of the molecule.
In addition, the geometry between the molecule-electrodes complex is influenced by aqueous and electrolytic environment, thermal phenomena, and the effects of the applied transverse as well as longitudinal (translocating) electric fields. With a low transverse voltage bias and picoampere (pA) and sub-pA tunneling currents, the main difficulty remains in the poor signal-to-noise ratio, which weakens the predictive power of distinguishing various nucleotides, or even detecting their presence. These uncertainties are the subject of recent controversy in the literature. See, for example, J. Lagerqvist et al, Phys. Rev. E, 76, 3 (2007) and R. Zikic et al., Phys. Rev. E 76, 2 (2007). Higher bias is unacceptable in an actual device realization. Besides other possible destructive and nonlinear effects, electric forces at the negatively charged backbone of a DNA molecule move the molecule toward the anode, thereby disabling the translocation.
Conductance measurements are most commonly performed using standard metallic probes, such as gold, See, for example, M. A. Reed et al., Science 278, 252 (1997). Unfortunately, when DNA segments are sandwiched between this type of large cross-section electrodes, the structural deformations at the interface between electrodes and the base pairs can cause unacceptable variations in the measured current. See, for example, K. Tagami et al., Jap. J. of App. Phys. 42, 5887 (2003) and K. Tagami, L. G. Wang, and M. Tsukada, Nano Letters 4, 209 (2004).
The interface sensitivity in quantum transport is not only limited to measuring the current across DNA, it is a universal effect that makes measurement in single molecules particularly difficult. For that reason, there is currently a strong interest in the development of an experimental apparatus that will alleviate the difficulty of controlling the coupling between the electrodes and the molecules. One attractive idea is to develop a system where the coupling between the molecule and the electrodes is better localized, in such a way as to ensure higher reproducibility of measured current-voltage curves.
For instance, advanced two-probe electric systems have been devised to measure geometrical and electronic properties of DNA and DNA derivatives. See, for example, K. Shimotani et al., J. of Chem. Phys. 118, 8016 (2003). In this device, the tip is replaced by a carbon nanotube in order to probe nanometer-scale samples, since the probe must have a radius of curvature smaller than the size of the samples.
Since carbon nanotubes (CNTs) were discovered in 1990 (S. Iijima, Nature 354, 56 (1991), intense research into their applications in various fields of materials science continues at a rapid pace. See, for example, J. Bernholc et al., Ann. Rev. of Mat. Res. 32, 347 (2002). One active area of research has been the application of CNT tips as precision nanotools for manipulating biological molecules. Such research has been primarily directed to deciphering the relationship between structure and function in molecules. CNT tips are of particular interest due, in part, to their high aspect ratio that allows for imaging with higher spatial resolution. See, for example, L. Q. Quo et al., Physica E, 27, 240 (2005) and L. Q. Quo et al., App. Surf. Sc. 228, 53 (2004).
The appeal of carbon nanotubes does not only stem from their unique morphology but also because their terminal ends can be conveniently functionalized by chemical modification. See, for example, M. Majumder, N. Chopra, and B. J. Hinds, J. Am. Chem. Soc. 127, 9062 (2005) and S. S. Wong et al., Nature 394, 52 (1998). End doping can be done during growth as long as the dopant has a surfactant behavior. Functionalization has been used, for example, to improve desired properties, such as increased coupling or decreased work function for field emission purposes. See, for example, J. C. Charlier et al., Nano Letters 2, 1191 (2002); V. Meunier et al., App. Phys. Lett. 81, 46 (2002), and A. Maiti et al. Phys. Rev. Lett. 87, 155502 (2001).
A CNT has also been used as an electrode for dielectrophoretic trapping of DNA molecules as a way for achieving a high enough field gradient for trapping purposes while using low trapping voltages. See, for example, S. Tuukkanen et al., Nano Letters 6, 1339 (2006). Single DNA chains have also been chemically grafted onto aligned CNT electrodes as part of an effort to develop DNA-CNT sensors of high sensitivity and selectivity. See, for example, P. G. He, and L. M. Dai, Chem. Comm., 3, 348 (2004).
Previous experimental achievements, like those cited above, typically involve covalent bonding between the CNT tip and the molecule of interest. However, covalent binding of the molecule to the electrode can be problematic if a process is to be performed on the molecule that requires its freedom of movement. For example, covalent binding of DNA to the electrode would not be permissible in an application wherein a conductivity measurement is also used as a sequencing method. In such an application, the DNA strand would need to have the freedom to be easily threaded inside a nanogap created between the nanotube electrodes.
There remains a need in the art for measuring the electron transport properties of molecules with greater precision. A method that could achieve this would provide several benefits including, for example, the ability to identify a molecule or distinguish one molecule from another.